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WO2009089810A1 - Production et utilisation de cyclodepsipeptide antitumoral - Google Patents

Production et utilisation de cyclodepsipeptide antitumoral Download PDF

Info

Publication number
WO2009089810A1
WO2009089810A1 PCT/DE2008/001915 DE2008001915W WO2009089810A1 WO 2009089810 A1 WO2009089810 A1 WO 2009089810A1 DE 2008001915 W DE2008001915 W DE 2008001915W WO 2009089810 A1 WO2009089810 A1 WO 2009089810A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
scopularid
fungus
compound
scopulariopsis
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/DE2008/001915
Other languages
German (de)
English (en)
Inventor
Johannes Imhoff
Zhiguo Yu
Gerhard Lang
Jutta Wiese
Holger Kalthoff
Stephanie Klose
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Leibnitz-Institut fur Meereswissenschaften
Original Assignee
Leibnitz-Institut fur Meereswissenschaften
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Leibnitz-Institut fur Meereswissenschaften filed Critical Leibnitz-Institut fur Meereswissenschaften
Priority to EP08871155.1A priority Critical patent/EP2229401B1/fr
Priority to ES08871155T priority patent/ES2436148T3/es
Priority to US12/863,319 priority patent/US8772445B2/en
Publication of WO2009089810A1 publication Critical patent/WO2009089810A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/15—Depsipeptides; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the invention relates to cyclic peptides which are suitable for the production of medicaments for the treatment of cancerous diseases.
  • the invention also relates to a process for the production of these compounds and to their use as medicaments.
  • actinomycin D which is produced by Streptomyces parvulus
  • Streptomyces parvulus is already being used as a drug for the treatment of cancer (BC Cancer Agency Cancer Drug Manual - 1994. http://www.bccancer.bc.ca/NR/rdonlyres/852AlFC3-5BD2- 481B-BFAA-45ACBFA77FAC / 22684 / Dactinomycinmonogra ⁇ h_5APR07. ⁇ df).
  • Thiocoralin a product of Micromonspora marina, inhibits the growth of tumor cells (Romero, F.
  • the present invention has for its object to provide other antitumoral peptides acting, and to show a way to their production.
  • the inventively preferred antitumoral peptides Scopularid A and Scopularid B were isolated from cultures of the fungus Scopulariopsis brevicaulis by preparative HPLC.
  • scopularide B shows significant inhibitory effects against tumor cell lines, in particular against pancreatic cancer cell line Colo357 (see Example 4).
  • inoculum for the experimental fungal culture was of a 14 day old pre-culture, which was grown on WM medium with a loopful of the cell material in the presence set of the main culture convicted.
  • the incubation of the inoculated nutrient solution was carried out over a period of 14 days at a constant 28 ° C in static culture in the dark.
  • the morphological characteristics of the fungus are determined by scanning electron microscopy.
  • the fungus shows individual conidiophores that emerge from hyphae.
  • the hyphae are unbranched, or divided vertically once or twice.
  • the conidiogenic cells are cylindrical, sometimes with a swollen base, and with a uniformly wide annealing zone of variable length.
  • the conidia are spherical to oval (4-6 x 6-7 microns) and have a flattened base and rough elevations.
  • Genetic identification is based on 18S rDNA analysis. The morphological characteristics and the 18S rDNA sequence give a clear identification of the fungus as Scopulariopsis brevicaulis.
  • the mushroom mycelium is separated from the culture supernatant, minced and extracted with acetone.
  • the acetone extract is evaporated to dryness and the residue is washed successively with a methanol-water mixture (2: 8) and with n-hexane.
  • the remaining residue is subjected to separation by preparative high performance liquid chromatography:
  • Scopularid A and Scopularid B showed significant inhibitory effects against tumor cell lines, in particular pancreatic cancer cell lines Colo357 and Panc89 and intestinal tumor cell line HT29 (on average between 25-50% inhibition at 10 ⁇ g / ml). This activity was determined by the crystal violet assay (Siegmund, D. et al., "Death receptor-induced signaling pathways are differentially regulated by gamma interferon upstream of caspase 8 processing.” Mol. Cell. Biol. 2005; 25: 6363-6379 ).

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

Composé de structure générale (I) dans laquelle R1, R2, R3 et R4 sont sélectionnés dans le groupe comprenant un atome d'hydrogène (H) et un alkyle en C1-C20, et R5 désigne un reste phényle.
PCT/DE2008/001915 2008-01-18 2008-11-20 Production et utilisation de cyclodepsipeptide antitumoral Ceased WO2009089810A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP08871155.1A EP2229401B1 (fr) 2008-01-18 2008-11-20 Production et utilisation de cyclodepsipeptide antitumoral
ES08871155T ES2436148T3 (es) 2008-01-18 2008-11-20 Preparación y uso de ciclodepsipéptidos antitumorales
US12/863,319 US8772445B2 (en) 2008-01-18 2008-11-20 Production and use of antitumoral cyclodepsipeptides

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102008005097.0 2008-01-18
DE102008005097A DE102008005097B4 (de) 2008-01-18 2008-01-18 Antitumoraler Cyclodepsipeptide, deren Herstellung und Verwendung

Publications (1)

Publication Number Publication Date
WO2009089810A1 true WO2009089810A1 (fr) 2009-07-23

Family

ID=40340661

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE2008/001915 Ceased WO2009089810A1 (fr) 2008-01-18 2008-11-20 Production et utilisation de cyclodepsipeptide antitumoral

Country Status (5)

Country Link
US (1) US8772445B2 (fr)
EP (1) EP2229401B1 (fr)
DE (1) DE102008005097B4 (fr)
ES (1) ES2436148T3 (fr)
WO (1) WO2009089810A1 (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004035613A2 (fr) * 2002-10-18 2004-04-29 Pharma Mar, S.A.U. Composes antitumoraux

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5270334A (en) * 1989-01-31 1993-12-14 E. R. Squibb & Sons, Inc. 4-methoxy-5-methyl-pyran-3-ol natural products and derivatives thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004035613A2 (fr) * 2002-10-18 2004-04-29 Pharma Mar, S.A.U. Composes antitumoraux

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
JIMENO JOSÉ ET AL: "Adding pharmacogenomics to the development of new marine-derived anticancer agents", JOURNAL OF TRANSLATIONAL MEDICINE, BIOMED CENTRAL, LONDON, GB, vol. 4, no. 1, 9 January 2006 (2006-01-09), pages 3, XP021009902, ISSN: 1479-5876 *
YU ZHIGUO ET AL: "Scopularides A and B, cyclodepsipeptides from a marine sponge-derived fungus, Scopulariopsis brevicaulis.", JOURNAL OF NATURAL PRODUCTS JUN 2008, vol. 71, no. 6, June 2008 (2008-06-01), pages 1052 - 1054, XP002514970, ISSN: 1520-6025 *

Also Published As

Publication number Publication date
US20110077205A1 (en) 2011-03-31
DE102008005097B4 (de) 2011-04-07
ES2436148T3 (es) 2013-12-27
EP2229401B1 (fr) 2013-08-21
US8772445B2 (en) 2014-07-08
DE102008005097A1 (de) 2009-07-23
EP2229401A1 (fr) 2010-09-22

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